Ultrasensitive electrochemical detection of methotrexate in biological fluids using NiMn₂O₄/CNT nanocomposite-modified electrode

Abstract

Methotrexate (MTX) is a widely used chemotherapeutic drug with a narrow therapeutic index, making its precise monitoring crucial for effective treatment and minimizing side effects. This study focuses on the development of a clinically applicable NiMn₂O₄/CNT nanocomposite-modified glassy carbon electrode (NiMn₂O₄/CNT-GCE) for the sensitive and selective electrochemical detection of MTX. The NiMn₂O₄ nanomaterial was synthesized via a co-precipitation method followed by calcination, and its composite with CNTs was optimized to enhance electrochemical performance. The sensor demonstrated a detection limit as low as 0.627 nM and a broad linear detection range (0.05–3 μM), attributed to the synergistic effects of NiMn₂O₄ and CNTs that enhance electron transfer and active site availability. Moreover, the NiMn₂O₄/CNT-GCE was successfully applied to detect MTX in spiked serum and urine samples, achieving recovery rates of 96–99% with relative standard deviations below 3.5%. Its minimal interference with common metabolites and excellent stability makes it ideal for therapeutic drug monitoring. This work underscores the potential of NiMn₂O₄/CNT as a promising platform for real-time clinical diagnostics and advanced electrochemical sensing applications.